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Keywords = collagen-based hydrogel

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25 pages, 8096 KB  
Article
Hydrophilic Anhydride-Containing Oligomers for Two-Component Hydrogels: From Biopolymer Compatibility to Cytocompatible Gelatin Bioinks
by Julia C. Matros, Katharina E. Wiebe-Ben Zakour, Joana Witt and Michael C. Hacker
Gels 2026, 12(5), 437; https://doi.org/10.3390/gels12050437 - 16 May 2026
Viewed by 284
Abstract
Tissue engineering represents a central strategy in regenerative medicine to restore damaged or missing tissue through structural and functional replacement. In this study, a two-component bioink platform was developed based on amine–anhydride conjugation as a mild crosslinking reaction between synthetic anhydride-containing oligomers (oSMoMA-x) [...] Read more.
Tissue engineering represents a central strategy in regenerative medicine to restore damaged or missing tissue through structural and functional replacement. In this study, a two-component bioink platform was developed based on amine–anhydride conjugation as a mild crosslinking reaction between synthetic anhydride-containing oligomers (oSMoMA-x) and natural biopolymers. The compatibility of the oligomers with different amine-containing biopolymers, including chitosan, gelatin, and hydrolyzed collagen peptides, was systematically evaluated. To improve cytocompatibility and enable controlled network formation, oSMoMA oligomers with varying anhydride contents were synthesized and characterized, allowing targeted tuning of material properties through comonomer composition. The resulting hydrogels were comparatively assessed with respect to their rheological and physicochemical properties. While hydrogel formation was achieved with all investigated biopolymers, gelatin-based systems exhibited the most favorable characteristics for bioink development. Two gelatin/oSMoMA bioink formulations with distinct gelation behavior were obtained by employing different base catalysts, enabling control over crosslinking kinetics and material properties. Cytocompatibility was comprehensively evaluated using viability assays, demonstrating enhanced metabolic activity of cells encapsulated in gelatin/oSMoMA-3.5 hydrogels compared to established reference systems, with sustained compatibility for up to seven days. Extrusion-based 3D bioprinting was performed using a modified printhead with integrated temperature control to maintain physiological conditions. The bioinks were successfully printed with embedded murine 3T3 fibroblasts, and post-printing analyses confirmed cell proliferation within the hydrogel constructs. Overall, the results demonstrate the broad compatibility of amin–anhydride-crosslinked oSMoMA systems with different biopolymers and highlight gelatin/oSMoMA bioinks as promising cytocompatible materials for stable 3D bioprinting applications in tissue engineering. Full article
(This article belongs to the Special Issue Gels in Tissue Engineering)
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26 pages, 12386 KB  
Article
Ameliorating Effects of the Hydrogel–Stem Cell–Melatonin Combination with or Without a Mesh to Treat Experimentally Induced Liver Degeneration in Rats
by Gokcen Ozgun, Deniz Yucel, Gozde Ervin Kole, Samed Ozer, Fatma Merve Antmen, Meltem Kolgazi, Nurdan Tozun and Serap Arbak
Life 2026, 16(5), 807; https://doi.org/10.3390/life16050807 (registering DOI) - 12 May 2026
Viewed by 158
Abstract
Objectives: This study aimed to investigate the therapeutic efficacy of a hydrogel loaded with Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) and melatonin, administered to the liver either via mesh–hydrogel implantation or intraperitoneal hydrogel injection, in a thioacetamide (TAA)-induced liver fibrosis animal model. Methods: [...] Read more.
Objectives: This study aimed to investigate the therapeutic efficacy of a hydrogel loaded with Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) and melatonin, administered to the liver either via mesh–hydrogel implantation or intraperitoneal hydrogel injection, in a thioacetamide (TAA)-induced liver fibrosis animal model. Methods: A collagen-based hydrogel containing WJ-MSCs and melatonin was prepared for injection as well as combined with electrospun mesh for implantation. Hydrogel and mesh were characterized with respect to morphology, degradation, and mechanical properties. In in vivo studies, liver fibrosis was induced in rats by intraperitoneal injection of TAA for 6 weeks. After fibrosis induction, animals received either hydrogel injection or implantation of the combined construct. After 21 days, serum and liver tissues were collected, and biochemical, histopathological, and ultrastructural analyses were performed through comparative evaluation of experimental groups. Results: SEM results demonstrated that hydrogel, with appropriate porosity, was well integrated with the mesh without any detachment. The mesh, composed of submicron-scale fibers, exhibited a Young’s modulus of 10.37 ± 2.33 MPa. The hydrogel presented a degradation profile with a 40% mass loss in 24 h, reaching approximately 50% by day 30. Biochemical results indicated significant improvement in liver regeneration with both treatment strategies, particularly with the implanted construct. Histopathological analysis revealed decreased inflammation and hepatocyte vacuolization following both treatments; however, collagen accumulation was significantly reduced in the implant group. Ultrastructural analysis showed preserved nuclear integrity and reduced endoplasmic reticulum dilation and degenerative changes in implant group. Conclusions: The combination of WJ-MSCs and melatonin-loaded hydrogel with supportive mesh particularly enhanced tissue regeneration in liver fibrosis. Full article
(This article belongs to the Section Pharmaceutical Science)
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20 pages, 4437 KB  
Article
hBM-MSC-Laden 3D Bioprinted Gelatin–Alginate Hydrogels: Physicochemical Characterisation and Osteogenic Lineage Commitment
by Devy F. Garna, Zetian Zhang and Lucy Di-Silvio
Gels 2026, 12(5), 387; https://doi.org/10.3390/gels12050387 - 1 May 2026
Viewed by 385
Abstract
Gelatin–alginate composite hydrogels are some of the most prevalent bioinks used for extrusion-based three-dimensional (3D) bioprinting because of their combined bioactivity and ability to ionically crosslink. Ionically crosslinked gelatin–alginate constructs containing human bone marrow–derived mesenchymal stem cells (hBM-MSCs) were characterised over time under [...] Read more.
Gelatin–alginate composite hydrogels are some of the most prevalent bioinks used for extrusion-based three-dimensional (3D) bioprinting because of their combined bioactivity and ability to ionically crosslink. Ionically crosslinked gelatin–alginate constructs containing human bone marrow–derived mesenchymal stem cells (hBM-MSCs) were characterised over time under standardised in vitro conditions to assess physicochemical properties and resultant cell behaviour. Water uptake and degradation were quantified over time in phosphate-buffered saline (PBS) and collagenase type II media for up to 21 days. Cell viability and metabolic activity were quantified, and osteogenic gene expression (RUNX2, COL1A1, OCN) was assessed. Raman spectroscopy and compressive mechanical characterisation were performed. Collagen and glycosaminoglycan-related peaks were observed from extracellular matrix (ECM)-associated components, with an increased presence of protein-associated signatures later in culture. Hydrogels displayed nonlinear elastic behaviour with increased stress after longer incubation times, suggesting no degradation of mechanical integrity over the duration of the study. Hydrogels experienced rapid hydration followed by decreased swelling over time, with a maximum swelling ratio at 24 h. Degradation rates significantly increased over longer incubation times (p < 0.001) and in collagenase media compared to PBS (p < 0.001). Observed differences were likely due to both ion-exchange-mediated network disassembly and the dissolution of gelatin components. Cell metabolic activity decreased under osteogenic culture conditions, while changes in osteogenic marker expression were sequential, suggesting a transition from proliferation to early osteogenic commitment in this 3D system. This work provides both physicochemical and biological characterisation of a commonly utilised gelatin–alginate bioink system, to provide future optimisations within the field of extrusion-based bone tissue engineering, a reproducible baseline for future optimisation of bioink systems in extrusion-based bone tissue engineering. Full article
(This article belongs to the Special Issue Gelatin-Based Materials for Tissue Engineering)
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21 pages, 4500 KB  
Article
3D Bioprinting of Blood Vessel Model for Improving Wound Healing
by Florin Iordache, Madalina Dulceanu, Alina Maria Holban, Alexandra Valentina Badaluta, Aurelia Magdalena Pisoschi, Bogdan Stefan Vasile, Bogdan Amuzescu and Carmen Curutiu
Int. J. Mol. Sci. 2026, 27(9), 4019; https://doi.org/10.3390/ijms27094019 - 30 Apr 2026
Viewed by 303
Abstract
Hydrogel-based stem cell therapy uses different stem cells and bioactive molecules for wound healing in the treatment of diabetes and chronic burn wounds by accelerating angiogenesis, collagen deposition, and inhibition of inflammatory responses. Artificial vessels have already been used for patients with cardiovascular [...] Read more.
Hydrogel-based stem cell therapy uses different stem cells and bioactive molecules for wound healing in the treatment of diabetes and chronic burn wounds by accelerating angiogenesis, collagen deposition, and inhibition of inflammatory responses. Artificial vessels have already been used for patients with cardiovascular diseases, but most of them are polymeric, which can cause thrombosis and restenosis. 3D bioprinting combines cells, growth factors, and biomaterials to create a setting in which cells grow and differentiate into native tissue-like structures. The current study aimed to create a model of blood vessels using collagen and hyaluronic acid hydrogel combined with endothelial and muscle progenitor cells derived from amniotic mesenchymal stem cells using 3D bioprinting. A computer-aided design (CAD) software was employed to create the 3D models of a blood vessel model and printed using a 3D bioprinter with two printheads: one with bioink encapsulating endothelial progenitor cells and the second with bioink encapsulating smooth muscle progenitor cells. The blood vessel constructs were characterized morphologically and structurally by Fourier Transform Infrared (FTIR) Spectroscopy, thermogravimetric analysis (TGA), Scanning Electron Microscopy (SEM), immunohistochemistry, water uptake, and enzymatic degradation. Viability, proliferation, oxidative stress, vascular endothelial growth factor (VEGF) and nitric oxide (NO) production were assessed to demonstrate the cytocompatibility of the blood vessel constructs. Our results showed that collagen–hyaluronic acid hydrogels embedded with stem cells can be used for vascular constructs, meeting the desired requirements of biocompatibility and accuracy in reproducing the model created in the CAD software v1.0. Full article
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24 pages, 23546 KB  
Article
Tendon dECM Composited with Chitosan with Loading Skin Precursor Stem Cell Exosome for Enhanced Diabetic Wound Healing
by Yunguang Chen, Yingying Liang, Yaling Deng and Lei Nie
Gels 2026, 12(5), 361; https://doi.org/10.3390/gels12050361 - 26 Apr 2026
Viewed by 243
Abstract
Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and [...] Read more.
Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (4th Edition))
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17 pages, 7069 KB  
Article
Optical and Thermal Control of Pore Architecture in Collagen Hydrogels for Vascular-like Tissue Engineering Scaffolds
by Mareni Arishima, Shigehisa Aoki, Sayaka Masaike and Takayuki Narita
Micro 2026, 6(2), 28; https://doi.org/10.3390/micro6020028 - 22 Apr 2026
Viewed by 320
Abstract
Vascularization remains a central challenge in thick tissue engineering. Building on our prior demonstration that carbonate buffer concentration governs multi-channel collagen gel (MCCG) architecture and perfusion culture performance, this study aimed to establish non-contact, orthogonal control of pore size and density in riboflavin-sensitized [...] Read more.
Vascularization remains a central challenge in thick tissue engineering. Building on our prior demonstration that carbonate buffer concentration governs multi-channel collagen gel (MCCG) architecture and perfusion culture performance, this study aimed to establish non-contact, orthogonal control of pore size and density in riboflavin-sensitized Type I collagen hydrogels via UV irradiation intensity and preparation temperature. UV intensity was modulated by varying the source-to-sample distance (25–52 mm); preparation temperature was set at 5, 25, or 40 °C; gelation kinetics were quantified using a vial-tilt assay. Pore area fraction ranged from 0.9% to 8.6% and Young’s modulus from 16 to 49 kPa depending on UV dose. Higher preparation temperatures accelerated gelation and produced smaller, more densely distributed pores, consistent with kinetically arrested phase separation. NIH/3T3 fibroblasts cultured on intermediate- and low-intensity UV scaffolds achieved >80% confluency by Day 7, with three-dimensional tissue-like organization and directionally aligned cellular bundles within large pores; cell metabolic activity, assessed by CCK-8 assay, remained consistently high throughout the culture period. These results demonstrate that UV irradiation intensity and preparation temperature are independently tunable, non-contact parameters for reproducible fabrication of collagen scaffolds with tunable vascular-like pore networks, complementing and extending the chemical (buffer concentration) design space of MCCG-based perfusion culture systems. Full article
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20 pages, 9395 KB  
Article
Collagen-Enriched Immunomodulatory Hydrogel for Tendon Regeneration
by Shivam Patel, Jeremy Pan, An Phong Nguyen, Nahid Howard and Finosh G. Thankam
Gels 2026, 12(4), 317; https://doi.org/10.3390/gels12040317 - 8 Apr 2026
Viewed by 638
Abstract
Rotator cuff tendon injury (RCTI) is aggravated by the pro-inflammatory milieu elicited by TLR4 and TREM1 signaling. Hence, tendon tissue engineering approaches require considerations that address these inflammatory episodes to benefit active regenerative responses. The objective of this study was to engineer and [...] Read more.
Rotator cuff tendon injury (RCTI) is aggravated by the pro-inflammatory milieu elicited by TLR4 and TREM1 signaling. Hence, tendon tissue engineering approaches require considerations that address these inflammatory episodes to benefit active regenerative responses. The objective of this study was to engineer and evaluate the immunocompatibility of a tendon-mimetic hydrogel composed of a chitosan–polyvinyl alcohol (PVA) blend incorporated with Collagen-I and to assess LR12 delivery for addressing TREM1-driven inflammation in RCTI management. A chitosan–PVA-HEMA-Acrylic acid (CPHA) hydrogel was synthesized by blending the linear natural polysaccharide chitosan and linear synthetic polymer PVA in an aqueous phase, followed by incorporation and redox chain growth with HEMA using acrylic acid (AA). Interpenetration of Collagen-I in CPHA yielded the CPHA-C hydrogel. CPHA and CPHA-C hydrogels displayed ample surface functional moieties provided by the co-polymers, exhibited excellent porosity as revealed by SEM imaging (28.65 ± 6.85 and 41.56 ± 18.00, respectively, for CPHA and CPHA-C), and were amphiphilic, as evident by contact angle analysis (~70 for CPHA and CPHA-C). Both hydrogels displayed a progressive release profile for the TREM1-inhibitory peptide LR12 for 7 days, whereas the LR12-loaded CPHA hydrogel exhibited increased TREM1 inhibition in LPS-challenged RAW264.7 macrophages. CPHA and CPHA-C hydrogels were immunocompatible and masked the oxidative damage in RAW264.7 macrophages, as evident by decreased levels of mitochondrial superoxide and ROS. Additionally, the CPHA hydrogel displayed an increased TGFβ/TLR4 ratio (0.24), whereas the CPHA-C (−0.52) system showed a decreased ratio upon exposure to tenocytes and macrophages. Overall, the findings highlight the potential of CPHA and CPHA-C hydrogels as candidates for tendon regenerative applications. Full article
(This article belongs to the Special Issue Novel Functional Gels for Biomedical Applications (2nd Edition))
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21 pages, 6168 KB  
Article
3D-Bioprinted Gelatin Hydrogels with Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Cutaneous Wound Healing In Vivo
by Manal Hussein Taghdi, Ibrahim N. Amirrah, Nurul Izzati Uda Zahli, Kavita Chirara, Mh Busra Fauzi, Jia Xian Law and Yogeswaran Lokanathan
Polymers 2026, 18(7), 882; https://doi.org/10.3390/polym18070882 - 3 Apr 2026
Viewed by 693
Abstract
Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are emerging as potent acellular therapeutics; however, their rapid clearance hinders their clinical translation. To address this issue, 3D-bioprinted genipin-crosslinked gelatin (GECL) was engineered for human health. GECL hydrogels were functionalised with human [...] Read more.
Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are emerging as potent acellular therapeutics; however, their rapid clearance hinders their clinical translation. To address this issue, 3D-bioprinted genipin-crosslinked gelatin (GECL) was engineered for human health. GECL hydrogels were functionalised with human umbilical cord MSC-derived sEVs (hUCMSC-sEVs) to create a bioactive wound-healing platform. These hydrogels demonstrated favourable physicochemical, mechanical, and biodegradable properties while providing an extracellular matrix (ECM)-mimetic environment conducive to tissue regeneration. MSCs were isolated from the umbilical cords, and their small extracellular vesicles (sEVs) were extracted and incorporated into gelatin-based hydrogels via 3D bioprinting. These sEV-loaded scaffolds were embedded in full-thickness wounds in mice, and healing was evaluated through macroscopic observation, histological analysis, collagen deposition, and angiogenesis assessment. Compared with the untreated controls, both the hydrogel-only (B) and sEV-loaded hydrogel (BE) groups significantly accelerated in vivo wound healing. Notably, the BE group achieved complete wound closure within 14 days, restoring the skin architecture, which closely resembled the native tissue with well-organised epidermal and dermal layers, optimal thickness, and skin appendages. Histological and ultrastructural assessments revealed an increased collagen type I deposition, a reduced α-smooth muscle actin (α-SMA) expression, and a robust neovascularisation. The TEM revealed tight junctions and active cellular infiltration, indicating scaffold integration and functional remodelling. Immunohistochemistry further revealed an upregulated CD31 expression with a balanced α-smooth muscle actin (α-SMA) expression, reflecting coordinated angiogenesis and myofibroblast regulation. These results highlight sEV-functionalised GECL hydrogels as robust and clinically translatable acellular therapeutic green products for accelerated wound closure and functional skin regeneration, advancing the fields of regenerative medicine and life expectancy. Full article
(This article belongs to the Special Issue Polymeric Materials for Wound Dressing)
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13 pages, 4598 KB  
Article
Human Nasal Cells in Nanofibrillar Cellulose Hydrogel: Viability, Function, and Implications for Bone Tissue Regeneration
by Marijana Sekulic, Alina Korah, Simona Negoias, Daniel Bodmer and Vesna Petkovic
Cells 2026, 15(7), 641; https://doi.org/10.3390/cells15070641 - 2 Apr 2026
Viewed by 572
Abstract
Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires [...] Read more.
Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article
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18 pages, 3767 KB  
Article
Formulation and 3D Printing of Collagen/Chitosan Inks: Tailoring the Scaffold Properties
by Teresa Carranza, Mireia Andonegui, Raquel Hernáez, Ana Aiastui, Yi Zhang, Koro de la Caba and Pedro Guerrero
Gels 2026, 12(3), 261; https://doi.org/10.3390/gels12030261 - 21 Mar 2026
Viewed by 551
Abstract
The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and [...] Read more.
The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and suitability for cartilage tissue engineering. Rheological analyses revealed that all samples exhibited shear-thinning behavior and solid-like viscoelasticity, with the formulation of an 80:20 COL/CHI ratio (20CHI) demonstrating optimal filament formation and dimensional stability. Physicochemical analyses confirmed the preservation of the collagen triple helix and the formation of hydrogen bonding between chitosan and collagen. 20CHI scaffolds showed swelling capacity and high cohesiveness. In vitro studies confirmed the cytocompatibility of the scaffolds with murine fibroblasts and the ability of the scaffolds to promote adhesion, proliferation, and extracellular matrix production of both chondrocytes and adipogenic mesenchymal stem cells (aMSCs). Quantification of sulfated glycosaminoglycan (sGAG) indicated sustained matrix deposition over 28 days, particularly by chondrocytes. These findings demonstrate that 20CHI hydrogel is a promising candidate for 3D printing of biomimetic scaffolds for cartilage regeneration. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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23 pages, 11154 KB  
Article
Oxidized Dextran/Carboxymethyl Chitosan Dynamic Schiff-Base Hydrogel for Sustained Hydrogen Sulfide Delivery and Burn Wound Microenvironment Remodeling
by Zhishan Liu, Ying Zhu, Zhuoya Ma, Xuyang Ning, Ziqiang Zhou, Jinchang Liu, Youfu Xie, Gang Li and Ping Hu
Pharmaceutics 2026, 18(3), 370; https://doi.org/10.3390/pharmaceutics18030370 - 17 Mar 2026
Viewed by 836
Abstract
Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate [...] Read more.
Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate hydrogel capable of sustained hydrogen sulfide (H2S) release for burn wound therapy, and to evaluate its physicochemical properties, in vivo efficacy, and mechanism of action. Methods: A dynamic hydrogel (ACMOD) was fabricated via Schiff-base crosslinking between oxidized dextran (OD) and carboxymethyl chitosan (CMCS), incorporating the H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH). Rheological and recovery tests characterized its mechanical and self-healing properties. Efficacy and mechanisms were assessed in a rat full-thickness burn model, analyzing wound closure, histology, oxidative stress, macrophage polarization, angiogenesis, and collagen deposition. Results: ACMOD exhibited shear-thinning, rapid self-healing, and strong tissue adherence. Sustained H2S release from ACMOD significantly accelerated wound closure and improved tissue regeneration compared to controls. Mechanistically, H2S attenuated oxidative stress, promoted a pro-regenerative M2 macrophage phenotype, enhanced angiogenesis via VEGF upregulation, and fostered organized collagen deposition and extracellular matrix remodeling. Conclusions: This work demonstrates a versatile, carbohydrate-based dynamic hydrogel platform that synergizes polymer network dynamics with bioactive H2S delivery to effectively promote burn wound healing. The findings underscore the potential of polysaccharide hydrogels with integrated gasotransmitter release for regenerative therapy and biomaterials applications. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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19 pages, 2801 KB  
Article
Improving Diffusion in Collagen Hydrogels for 3D Culture of Rat Cardiac or Dermal Fibroblasts via Magnetically Actuated Vibrating Microparts
by Kenji Inoue, Zhonggang Feng, Yuta Higashiyama, Toshifumi Kawaguchi, Takehiro Matsuura and Masaharu Abe
Gels 2026, 12(3), 225; https://doi.org/10.3390/gels12030225 - 10 Mar 2026
Viewed by 413
Abstract
Ensuring efficient nutrient delivery and waste removal within the interior of three-dimensional (3D) cultures remains a major challenge in tissue engineering. Here, we demonstrate a proof-of-concept methodology that creates internally distributed driving sources to enhance diffusion and perfusion within 3D constructs. Iron microparticles [...] Read more.
Ensuring efficient nutrient delivery and waste removal within the interior of three-dimensional (3D) cultures remains a major challenge in tissue engineering. Here, we demonstrate a proof-of-concept methodology that creates internally distributed driving sources to enhance diffusion and perfusion within 3D constructs. Iron microparticles or iron-containing microtubes were incorporated into collagen gels used for the 3D culture of dermal or cardiac fibroblasts, and cyclic dynamic magnetic fields were applied to the constructs. Oscillatory motion of the iron particles enhanced diffusion within the gels, as evidenced by increases in the fast diffusion coefficient of more than threefold and the slow diffusion coefficient of more than tenfold under conditions suitable for cell culture. In cardiac fibroblast cultures, this enhancement significantly increased proliferation by approximately twofold and reduced cytotoxicity by half compared with controls. In contrast, no significant effects were observed in dermal fibroblast cultures. Cyclic compression of microtubes within the collagen gels induced by dynamic magnetic fields primarily resulted in cellular morphological changes, including a reduction in cell area to approximately 0.8-fold of the control values, increased cell polarization with the cellular aspect ratio rising from 1.4 to 1.9, and preferred cell orientations either parallel or perpendicular to the microtube axis. Together, these results suggest that this methodology has the potential to be developed as an effective strategy for improving diffusivity in 3D metabolic environments and for promoting angiogenesis in hydrogel-based cultures. Full article
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17 pages, 1303 KB  
Review
Chondrogenesis of Peripheral Blood-Derived Mesenchymal Stromal Cells
by Harish V. K. Ratna, Madhan Jeyaraman, Naveen Jeyaraman, Arulkumar Nallakumarasamy, Luise Schäfer, Filippo Migliorini and Sathish Muthu
Cells 2026, 15(5), 476; https://doi.org/10.3390/cells15050476 - 6 Mar 2026
Viewed by 898
Abstract
Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted [...] Read more.
Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105+ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article
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21 pages, 15875 KB  
Article
Glycogen Hydrogel Loaded with Schistosoma japonicas Peptide SJMHE1 Improves Skin Wound Healing
by Yanwei Yang, Shang Wang, Yuyun Jiang, Liyue Huo, Wei Zhu, Xiaolin Zhang, Yubei Zhang and Xuefeng Wang
Biomolecules 2026, 16(3), 392; https://doi.org/10.3390/biom16030392 - 5 Mar 2026
Viewed by 652
Abstract
Current wound healing strategies must confront numerous challenges. Helminth-induced immunomodulation offers a promising therapeutic avenue for inflammatory diseases and injury repair. However, research on the role of helminths in damage recovery remains limited. We utilized glycogen—a naturally occurring biomaterial—to encapsulate SJMHE1, a bioactive [...] Read more.
Current wound healing strategies must confront numerous challenges. Helminth-induced immunomodulation offers a promising therapeutic avenue for inflammatory diseases and injury repair. However, research on the role of helminths in damage recovery remains limited. We utilized glycogen—a naturally occurring biomaterial—to encapsulate SJMHE1, a bioactive peptide derived from Schistosoma japonicum, and successfully developed a facilely prepared hydrogel formulation denoted as SJMHE1-gel. The properties of SJMHE1-gel, its effect on cell activity, and its performance in a murine full-thickness skin defect model were evaluated. The glycogen-based hydrogel exhibited a uniform pore size, excellent biocompatibility, and sustained release of SJMHE1. Topical application of SJMHE1-gel enhanced collagen deposition, promoted angiogenesis, facilitated the regeneration of hair follicles and sebaceous glands, and accelerated full-thickness wound healing. SJMHE1-gel also promoted M2 macrophage polarisation and suppressed inflammatory cytokine expression both in vivo and in vitro. Mechanistically, SJMHE1-treated macrophages upregulate TGF-β, which in turn promotes the migration of L929 fibroblasts and human umbilical vein endothelial cells (HUVECs) via the Smad3 pathway. Neutralization of TGF-β attenuates phosphorylated Smad3 (p-Smad3) levels and impairs the migratory capacity of both fibroblasts and HUVECs. Additionally, SJMHE1-treated macrophages upregulate VEGFA, thereby enhancing angiogenic tube formation in HUVECs. This easy-to-prepare hydrogel can regulate macrophage polarization, inhibit inflammation, promote angiogenesis, and accelerate collagen deposition, acting across wound healing stages to provide a novel therapeutic strategy. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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Article
Injectable Thermosensitive Composite Hydrogels for Sustained Nanoparticle Delivery and Enhanced Wound Healing
by Yiting Qiu, Zhiyun Cheng, Meiyan Liu, Dagui Zhang, Xia Gao, Longxiang Feng, Xianxiang Xu, Haoyang You, Xunxun Wu and Yong Diao
Gels 2026, 12(3), 191; https://doi.org/10.3390/gels12030191 - 25 Feb 2026
Viewed by 751
Abstract
Wound healing is frequently compromised by excessive oxidative stress, prolonged inflammation, and inadequate tissue regenerative capacity. To address these challenges, a thermosensitive and injectable composite hydrogel based on Pluronic F127 (F127), phosphatidylcholine (PC), and L-lysine (Lys) was developed for the sustained delivery of [...] Read more.
Wound healing is frequently compromised by excessive oxidative stress, prolonged inflammation, and inadequate tissue regenerative capacity. To address these challenges, a thermosensitive and injectable composite hydrogel based on Pluronic F127 (F127), phosphatidylcholine (PC), and L-lysine (Lys) was developed for the sustained delivery of sinomenine–gallic acid nanoparticles (SGNPs) and the acceleration of wound repair. The hydrogel undergoes a rapid sol–gel transition at physiological temperatures through physical interactions, enabling excellent injectability and in situ gelation. The optimized composite hydrogel exhibited improved mechanical properties, enhanced structural stability, and a uniform porous microarchitecture. The F127−Lys−PCF127−Lys−PC@SGNPs hydrogel showed superior overall stability and hemocompatibility while enabling the sustained release of SGNPs for up to 24 h. Benefiting from the incorporation of SGNPs, the composite hydrogel displayed enhanced antioxidant activity, effectively scavenging free radicals and alleviating cellular oxidative stress. In vitro experiments demonstrated that the hydrogel promoted keratinocyte migration and proliferation. Furthermore, in a murine full-thickness skin wound model, treatment with F127−Lys−PCF127−Lys−PC@SGNPs significantly accelerated wound closure and facilitated re-epithelialization, angiogenesis, and collagen deposition. Collectively, this multifunctional thermosensitive hydrogel provides a promising platform for advanced wound dressings that integrate sustained delivery, antioxidant protection, and tissue regeneration. Full article
(This article belongs to the Section Gel Processing and Engineering)
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